Arrested Development fans who like elephants, this is your story. An elephant named Koshik can mimic about seven words of Korean, and one of those words is “annyong,” or “hello.” It’s not unheard of for elephants to mimic sounds, but Koshik, who makes his Korean sounds by putting his trunk in his mouth, is the only living elephant who can mimic human speech in this way, according to researchers. You can hear Koshik making his sounds in the video, but unfortunately, it does not feature his saying “annyang.”

Koshik resides in a theme park in Korea. His technique and ability to mimic human speech have attracted researchers, who want to know more about how an animal without lips like ours could figure out a way to make our sounds. African elephants living around humans and our noises have been known to mimic human-related sounds like truck engines revving, and according to a CBS news report, an Asian elephant that lived in a zoo in Kazakhstan might have imitated sounds from the Kazahk and Russian languages. One African elephant who lived with two female Asian elephants at a zoo became known for using the chirpy mating calls of the Asian elephant instead of the lower-frequency vocalizations of the African elephant. The fellow had to do adjust, evidently. Koshik is a 20-year-old Asian elephant.

When you think about animals that mimic human speech, like crows, elephants, and possibly a beluga whale, think about what they have in common with us: They live in complex social groups where communication skills are important. Perhaps they adjust to their social environment, at least sometimes, by mimicking the sounds they hear. Koshik was so good at it that when Korean speakers came in as stenographers for his communication, they could clearly distinguish his words in Korean.

You may have had the experience: A medication you and a friend both take causes terrible side effects in you, but your friend experiences none. (The running joke in our house is, if a drug has a side-effect, we’ve had it.) How does that happen, and why would a drug that’s meant to, say, stabilize insulin levels, produce terrible gastrointestinal side effects, too? A combination of techy-tech scientific approaches might help answer those questions for you — and lead to some solutions.

It’s no secret I love lab technology. I’m a technophile. A geek. I call my web site “Biotechnically Speaking.” So when I saw this paper in the September issue of Nature Biotechnology, well, I just had to write about it.

The paper is entitled, “Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators.” If you read that and your eyes glazed over, don’t worry –- the article is way more interesting than its title.

Those trees on the right are called SPADE trees. They map cellular responses to different stimuli in a collection of human blood cells. Credit: (c) 2012 Nature America [Nat Biotechnol, 30:858--67, 2012]

Here’s the basic idea: The current methods drug developers use to screen potential drug compounds –- typically a blend of high-throughput imaging and biochemical assays – aren’t perfect. If they were, drugs wouldn’t fail late in development. Stanford immunologist Garry Nolan and his team, led by postdoc Bernd Bodenmiller (who now runs his own lab in Zurich), figured part of that problem stems from the fact that most early drug testing is done on immortalized cell lines, rather than “normal” human cells. Furthermore, the tests that are run on those cells aren’t as comprehensive as they could be, meaning potential collateral effects of the compounds might be missed. Nolan wanted to show that flow cytometry, a cell-analysis technique frequently used in immunology labs, can help reduce that failure rate by measuring drug impacts more holistically.

Nolan is a flow cytometry master. As he told me in 2010, he’s been using the technique for more than three decades, and even used a machine now housed in the Smithsonian.

In flow cytometry, researchers treat cells with reagents called antibodies, which are immune system proteins that recognize and bind to specific proteins on cell surfaces. Each type of cell has a unique collection of these proteins, and by studying those collections, it is possible to differentiate and count the different populations.

Suppose researchers wanted to know how many T cells of a specific type were present in a patient’s blood. They might treat those cells with antibodies that recognize a protein known as CD3 to pick those out. By adding additional antibodies, they can then select different T-cell subpopulations, such as CD4-positive helper T cells and CD8-positive cytotoxic T cells, both of which help you mount immune responses.

Cells of the immune systemSource: http://stemcells.nih.gov/info/scireport/chapter6.asp

In a basic flow cytometry experiment, each antibody is labeled with a unique fluorescent dye –- the antibody targeting CD3 might be red, say, and the CD4 antibody, green. The cells stream past a laser, one by one. The laser (or lasers –- there can be as many as seven) excites the dye molecules decorating the cell surface, causing them to fluoresce. Detectors capture that light and give a count of how many total cells were measured and the types of cells. The result is a kind of catalog of the cell population. For immune cells, for example, that could be the number of T cells, B cells (which, among other things, help you “remember” previous invaders), and macrophages (the big cells that chomp up invaders and infected cells). By comparing the cellular catalogs that result under different conditions, researchers gain insight into development, disease, and the impact of drugs, among other things.

But here’s the problem: Fluorescent dyes aren’t lasers, producing light of exactly one particular color. They absorb and emit light over a range of colors, called a spectrum. And those spectra can overlap, such that when a researcher thinks she’s counting CD4 T cells, she may actually be counting some macrophages. That overlap leads to all sorts of experimental optimization issues. An exceptionally talented flow cytometrist can assemble panels of perhaps 12 or so dyes, but it might take months to get everything just right.

That’s where the mass cytometry comes in. Commercialized by DVS Sciences, mass cytometry is essentially the love-chid of flow cytometry and mass spectrometry, combining the one-cell-at-a-time analysis of the former with the atomic precision of the latter. Mass spectrometry identifies molecules based on the ratio of their mass to their charge. In DVS’ CyTOF mass cytometer, a flowing stream of cells is analyzed not by shining a laser on them, but by nuking them in superhot plasma. The nuking reduces the cell to its atomic components, which the CyTOF then measures.

Specifically, the CyTOF looks for heavy atoms called lanthanides, elements found in the first of the two bottom rows of the periodic table, like gadolinium, neodymium, and europium. These elements never naturally occur in biological systems and so make useful cellular labels. More to the point, the mass spectrometer is specific enough that these signals basically don’t overlap. The instrument will never confuse gadolinium for neodymium, for instance. Researchers simply tag their antibodies with lanthanides rather than fluorophores, and voila! Instant antibody panel, no (or little) optimization required.

Now back to the paper. Nolan (who sits on DVS Sciences’ Scientific Advisory Board) and Bodenmiller wanted to see if mass cytometry could provide the sort of high-density, high-throughput cellular profiling that is required for drug development. The team took blood cells from eight donors, treated them with more than two dozen different drugs over a range of concentrations, added a dozen stimuli to which blood cells can be exposed in the body, and essentially asked, for each of the pathways we want to study, in each kind of cell in these patients’ blood, what did the drug do?

To figure that out, they used a panel of 31 lanthanides –- 10 to sort out the cell types they were looking at in each sample, 14 to monitor cellular signaling pathways, and 7 to identify each sample.

I love that last part, about identifying the samples. The numbers in this experiment are kind of staggering: 12 stimuli x 8 doses x 14 cell types x 14 intracellular markers per drug, times 27 drugs, is more than half-a-million pieces of data. To make life easier on themselves, the researchers pooled samples 96 at a time in individual tubes, adding a “barcode” to uniquely identify each one. That barcode (called a “mass-tag cellular barcode,” or MCB) is essentially a 7-bit binary number made of lanthanides rather than ones and zeroes: one sample would have none of the 7 reserved markers (0000000); one sample would have one marker (0000001); another would have another (0000010); and so on. Seven lanthanides produce 128 possible combinations, so it’s no sweat to pool 96. They simply mix those samples in a single tube and let the computer sort everything out later.

When all was said and done, the team was able to draw some conclusions about drug specificity, person-to-person variation, cell signaling, and more. Basically, and not surprisingly, some of the drugs they looked at are less specific than originally thought -– that is, they affect their intended targets, but other pathways as well. That goes a long way towards explaining side effects. But more to the point, they proved that their approach may be used to drive drug-screening experiments.

The four basic categories of molecules for building life are carbohydrates, lipids, proteins, and nucleic acids.

Carbohydrates serve many purposes, from energy to structure to chemical communication, as monomers or polymers.

Lipids, which are hydrophobic, also have different purposes, including energy storage, structure, and signaling.

Proteins, made of amino acids in up to four structural levels, are involved in just about every process of life.

The nucleic acids DNA and RNA consist of four nucleotide building blocks, and each has different purposes.

The longer version

Life is so diverse and unwieldy, it may surprise you to learn that we can break it down into four basic categories of molecules. Possibly even more implausible is the fact that two of these categories of large molecules themselves break down into a surprisingly small number of building blocks. The proteins that make up all of the living things on this planet and ensure their appropriate structure and smooth function consist of only 20 different kinds of building blocks. Nucleic acids, specifically DNA, are even more basic: only four different kinds of molecules provide the materials to build the countless different genetic codes that translate into all the different walking, swimming, crawling, oozing, and/or photosynthesizing organisms that populate the third rock from the Sun.

Big Molecules with Small Building Blocks

The functional groups, assembled into building blocks on backbones of carbon atoms, can be bonded together to yield large molecules that we classify into four basic categories. These molecules, in many different permutations, are the basis for the diversity that we see among living things. They can consist of thousands of atoms, but only a handful of different kinds of atoms form them. It’s like building apartment buildings using a small selection of different materials: bricks, mortar, iron, glass, and wood. Arranged in different ways, these few materials can yield a huge variety of structures.

We encountered functional groups and the SPHONC in Chapter 3. These components form the four categories of molecules of life. These Big Four biological molecules are carbohydrates, lipids, proteins, and nucleic acids. They can have many roles, from giving an organism structure to being involved in one of the millions of processes of living. Let’s meet each category individually and discover the basic roles of each in the structure and function of life.

Carbohydrates

You have met carbohydrates before, whether you know it or not. We refer to them casually as “sugars,” molecules made of carbon, hydrogen, and oxygen. A sugar molecule has a carbon backbone, usually five or six carbons in the ones we’ll discuss here, but it can be as few as three. Sugar molecules can link together in pairs or in chains or branching “trees,” either for structure or energy storage.

When you look on a nutrition label, you’ll see reference to “sugars.” That term includes carbohydrates that provide energy, which we get from breaking the chemical bonds in a sugar called glucose. The “sugars” on a nutrition label also include those that give structure to a plant, which we call fiber. Both are important nutrients for people.

Sugars serve many purposes. They give crunch to the cell walls of a plant or the exoskeleton of a beetle and chemical energy to the marathon runner. When attached to other molecules, like proteins or fats, they aid in communication between cells. But before we get any further into their uses, let’s talk structure.

The sugars we encounter most in basic biology have their five or six carbons linked together in a ring. There’s no need to dive deep into organic chemistry, but there are a couple of essential things to know to interpret the standard representations of these molecules.

Check out the sugars depicted in the figure. The top-left molecule, glucose, has six carbons, which have been numbered. The sugar to its right is the same glucose, with all but one “C” removed. The other five carbons are still there but are inferred using the conventions of organic chemistry: Anywhere there is a corner, there’s a carbon unless otherwise indicated. It might be a good exercise for you to add in a “C” over each corner so that you gain a good understanding of this convention. You should end up adding in five carbon symbols; the sixth is already given because that is conventionally included when it occurs outside of the ring.

On the left is a glucose with all of its carbons indicated. They’re also numbered, which is important to understand now for information that comes later. On the right is the same molecule, glucose, without the carbons indicated (except for the sixth one). Wherever there is a corner, there is a carbon, unless otherwise indicated (as with the oxygen). On the bottom left is ribose, the sugar found in RNA. The sugar on the bottom right is deoxyribose. Note that at carbon 2 (*), the ribose and deoxyribose differ by a single oxygen.

The lower left sugar in the figure is a ribose. In this depiction, the carbons, except the one outside of the ring, have not been drawn in, and they are not numbered. This is the standard way sugars are presented in texts. Can you tell how many carbons there are in this sugar? Count the corners and don’t forget the one that’s already indicated!

If you said “five,” you are right. Ribose is a pentose (pent = five) and happens to be the sugar present in ribonucleic acid, or RNA. Think to yourself what the sugar might be in deoxyribonucleic acid, or DNA. If you thought, deoxyribose, you’d be right.

The fourth sugar given in the figure is a deoxyribose. In organic chemistry, it’s not enough to know that corners indicate carbons. Each carbon also has a specific number, which becomes important in discussions of nucleic acids. Luckily, we get to keep our carbon counting pretty simple in basic biology. To count carbons, you start with the carbon to the right of the non-carbon corner of the molecule. The deoxyribose or ribose always looks to me like a little cupcake with a cherry on top. The “cherry” is an oxygen. To the right of that oxygen, we start counting carbons, so that corner to the right of the “cherry” is the first carbon. Now, keep counting. Here’s a little test: What is hanging down from carbon 2 of the deoxyribose?

If you said a hydrogen (H), you are right! Now, compare the deoxyribose to the ribose. Do you see the difference in what hangs off of the carbon 2 of each sugar? You’ll see that the carbon 2 of ribose has an –OH, rather than an H. The reason the deoxyribose is called that is because the O on the second carbon of the ribose has been removed, leaving a “deoxyed” ribose. This tiny distinction between the sugars used in DNA and RNA is significant enough in biology that we use it to distinguish the two nucleic acids.

In fact, these subtle differences in sugars mean big differences for many biological molecules. Below, you’ll find a couple of ways that apparently small changes in a sugar molecule can mean big changes in what it does. These little changes make the difference between a delicious sugar cookie and the crunchy exoskeleton of a dung beetle.

Sugar and Fuel

A marathon runner keeps fuel on hand in the form of “carbs,” or sugars. These fuels provide the marathoner’s straining body with the energy it needs to keep the muscles pumping. When we take in sugar like this, it often comes in the form of glucose molecules attached together in a polymer called starch. We are especially equipped to start breaking off individual glucose molecules the minute we start chewing on a starch.

Double X Extra: A monomer is a building block (mono = one) and a polymer is a chain of monomers. With a few dozen monomers or building blocks, we get millions of different polymers. That may sound nutty until you think of the infinity of values that can be built using only the numbers 0 through 9 as building blocks or the intricate programming that is done using only a binary code of zeros and ones in different combinations.

Our bodies then can rapidly take the single molecules, or monomers, into cells and crack open the chemical bonds to transform the energy for use. The bonds of a sugar are packed with chemical energy that we capture to build a different kind of energy-containing molecule that our muscles access easily. Most species rely on this process of capturing energy from sugars and transforming it for specific purposes.

Polysaccharides: Fuel and Form

Plants use the Sun’s energy to make their own glucose, and starch is actually a plant’s way of storing up that sugar. Potatoes, for example, are quite good at packing away tons of glucose molecules and are known to dieticians as a “starchy” vegetable. The glucose molecules in starch are packed fairly closely together. A string of sugar molecules bonded together through dehydration synthesis, as they are in starch, is a polymer called a polysaccharide (poly = many; saccharide = sugar). When the monomers of the polysaccharide are released, as when our bodies break them up, the reaction that releases them is called hydrolysis.

Double X Extra: The specific reaction that hooks one monomer to another in a covalent bond is called dehydration synthesis because in making the bond–synthesizing the larger molecule–a molecule of water is removed (dehydration). The reverse is hydrolysis (hydro = water; lysis = breaking), which breaks the covalent bond by the addition of a molecule of water.

Although plants make their own glucose and animals acquire it by eating the plants, animals can also package away the glucose they eat for later use. Animals, including humans, store glucose in a polysaccharide called glycogen, which is more branched than starch. In us, we build this energy reserve primarily in the liver and access it when our glucose levels drop.

Whether starch or glycogen, the glucose molecules that are stored are bonded together so that all of the molecules are oriented the same way. If you view the sixth carbon of the glucose to be a “carbon flag,” you’ll see in the figure that all of the glucose molecules in starch are oriented with their carbon flags on the upper left.

The orientation of monomers of glucose in polysaccharides can make a big difference in the use of the polymer. The glucoses in the molecule on the top are all oriented “up” and form starch. The glucoses in the molecule on the bottom alternate orientation to form cellulose, which is quite different in its function from starch.

Storing up sugars for fuel and using them as fuel isn’t the end of the uses of sugar. In fact, sugars serve as structural molecules in a huge variety of organisms, including fungi, bacteria, plants, and insects.

The primary structural role of a sugar is as a component of the cell wall, giving the organism support against gravity. In plants, the familiar old glucose molecule serves as one building block of the plant cell wall, but with a catch: The molecules are oriented in an alternating up-down fashion. The resulting structural sugar is called cellulose.

That simple difference in orientation means the difference between a polysaccharide as fuel for us and a polysaccharide as structure. Insects take it step further with the polysaccharide that makes up their exoskeleton, or outer shell. Once again, the building block is glucose, arranged as it is in cellulose, in an alternating conformation. But in insects, each glucose has a little extra added on, a chemical group called an N-acetyl group. This addition of a single functional group alters the use of cellulose and turns it into a structural molecule that gives bugs that special crunchy sound when you accidentally…ahem…step on them.

These variations on the simple theme of a basic carbon-ring-as-building-block occur again and again in biological systems. In addition to serving roles in structure and as fuel, sugars also play a role in function. The attachment of subtly different sugar molecules to a protein or a lipid is one way cells communicate chemically with one another in refined, regulated interactions. It’s as though the cells talk with each other using a specialized, sugar-based vocabulary. Typically, cells display these sugary messages to the outside world, making them available to other cells that can recognize the molecular language.

Lipids: The Fatty Trifecta

Starch makes for good, accessible fuel, something that we immediately attack chemically and break up for quick energy. But fats are energy that we are supposed to bank away for a good long time and break out in times of deprivation. Like sugars, fats serve several purposes, including as a dense source of energy and as a universal structural component of cell membranes everywhere.

Fats: the Good, the Bad, the Neutral

Turn again to a nutrition label, and you’ll see a few references to fats, also known as lipids. (Fats are slightly less confusing that sugars in that they have only two names.) The label may break down fats into categories, including trans fats, saturated fats, unsaturated fats, and cholesterol. You may have learned that trans fats are “bad” and that there is good cholesterol and bad cholesterol, but what does it all mean?

Let’s start with what we mean when we say saturated fat. The question is, saturated with what? There is a specific kind of dietary fat call the triglyceride. As its name implies, it has a structural motif in which something is repeated three times. That something is a chain of carbons and hydrogens, hanging off in triplicate from a head made of glycerol, as the figure shows. Those three carbon-hydrogen chains, or fatty acids, are the “tri” in a triglyceride. Chains like this can be many carbons long.

Double X Extra: We call a fatty acid a fatty acid because it’s got a carboxylic acid attached to a fatty tail. A triglyceride consists of three of these fatty acids attached to a molecule called glycerol. Our dietary fat primarily consists of these triglycerides.

Triglycerides come in several forms. You may recall that carbon can form several different kinds of bonds, including single bonds, as with hydrogen, and double bonds, as with itself. A chain of carbon and hydrogens can have every single available carbon bond taken by a hydrogen in single covalent bond. This scenario of hydrogen saturation yields a saturated fat. The fat is saturated to its fullest with every covalent bond taken by hydrogens single bonded to the carbons.

Saturated fats have predictable characteristics. They lie flat easily and stick to each other, meaning that at room temperature, they form a dense solid. You will realize this if you find a little bit of fat on you to pinch. Does it feel pretty solid? That’s because animal fat is saturated fat. The fat on a steak is also solid at room temperature, and in fact, it takes a pretty high heat to loosen it up enough to become liquid. Animals are not the only organisms that produce saturated fat–avocados and coconuts also are known for their saturated fat content.

The top graphic above depicts a triglyceride with the glycerol, acid, and three hydrocarbon tails. The tails of this saturated fat, with every possible hydrogen space occupied, lie comparatively flat on one another, and this kind of fat is solid at room temperature. The fat on the bottom, however, is unsaturated, with bends or kinks wherever two carbons have double bonded, booting a couple of hydrogens and making this fat unsaturated, or lacking some hydrogens. Because of the space between the bumps, this fat is probably not solid at room temperature, but liquid.

You can probably now guess what an unsaturated fat is–one that has one or more hydrogens missing. Instead of single bonding with hydrogens at every available space, two or more carbons in an unsaturated fat chain will form a double bond with carbon, leaving no space for a hydrogen. Because some carbons in the chain share two pairs of electrons, they physically draw closer to one another than they do in a single bond. This tighter bonding result in a “kink” in the fatty acid chain.

In a fat with these kinks, the three fatty acids don’t lie as densely packed with each other as they do in a saturated fat. The kinks leave spaces between them. Thus, unsaturated fats are less dense than saturated fats and often will be liquid at room temperature. A good example of a liquid unsaturated fat at room temperature is canola oil.

A few decades ago, food scientists discovered that unsaturated fats could be resaturated or hydrogenated to behave more like saturated fats and have a longer shelf life. The process of hydrogenation–adding in hydrogens–yields trans fat. This kind of processed fat is now frowned upon and is being removed from many foods because of its associations with adverse health effects. If you check a food label and it lists among the ingredients “partially hydrogenated” oils, that can mean that the food contains trans fat.

Double X Extra: A triglyceride can have up to three different fatty acids attached to it. Canola oil, for example, consists primarily of oleic acid, linoleic acid, and linolenic acid, all of which are unsaturated fatty acids with 18 carbons in their chains.

Why do we take in fat anyway? Fat is a necessary nutrient for everything from our nervous systems to our circulatory health. It also, under appropriate conditions, is an excellent way to store up densely packaged energy for the times when stores are running low. We really can’t live very well without it.

Phospholipids: An Abundant Fat

You may have heard that oil and water don’t mix, and indeed, it is something you can observe for yourself. Drop a pat of butter–pure saturated fat–into a bowl of water and watch it just sit there. Even if you try mixing it with a spoon, it will just sit there. Now, drop a spoon of salt into the water and stir it a bit. The salt seems to vanish. You’ve just illustrated the difference between a water-fearing (hydrophobic) and a water-loving (hydrophilic) substance.

Generally speaking, compounds that have an unequal sharing of electrons (like ions or anything with a covalent bond between oxygen and hydrogen or nitrogen and hydrogen) will be hydrophilic. The reason is that a charge or an unequal electron sharing gives the molecule polarity that allows it to interact with water through hydrogen bonds. A fat, however, consists largely of hydrogen and carbon in those long chains. Carbon and hydrogen have roughly equivalent electronegativities, and their electron-sharing relationship is relatively nonpolar. Fat, lacking in polarity, doesn’t interact with water. As the butter demonstrated, it just sits there.

There is one exception to that little maxim about fat and water, and that exception is the phospholipid. This lipid has a special structure that makes it just right for the job it does: forming the membranes of cells. A phospholipid consists of a polar phosphate head–P and O don’t share equally–and a couple of nonpolar hydrocarbon tails, as the figure shows. If you look at the figure, you’ll see that one of the two tails has a little kick in it, thanks to a double bond between the two carbons there.

Phospholipids form a double layer and are the major structural components of cell membranes. Their bend, or kick, in one of the hydrocarbon tails helps ensure fluidity of the cell membrane. The molecules are bipolar, with hydrophilic heads for interacting with the internal and external watery environments of the cell and hydrophobic tails that help cell membranes behave as general security guards.

The kick and the bipolar (hydrophobic and hydrophilic) nature of the phospholipid make it the perfect molecule for building a cell membrane. A cell needs a watery outside to survive. It also needs a watery inside to survive. Thus, it must face the inside and outside worlds with something that interacts well with water. But it also must protect itself against unwanted intruders, providing a barrier that keeps unwanted things out and keeps necessary molecules in.

Phospholipids achieve it all. They assemble into a double layer around a cell but orient to allow interaction with the watery external and internal environments. On the layer facing the inside of the cell, the phospholipids orient their polar, hydrophilic heads to the watery inner environment and their tails away from it. On the layer to the outside of the cell, they do the same.

As the figure shows, the result is a double layer of phospholipids with each layer facing a polar, hydrophilic head to the watery environments. The tails of each layer face one another. They form a hydrophobic, fatty moat around a cell that serves as a general gatekeeper, much in the way that your skin does for you. Charged particles cannot simply slip across this fatty moat because they can’t interact with it. And to keep the fat fluid, one tail of each phospholipid has that little kick, giving the cell membrane a fluid, liquidy flow and keeping it from being solid and unforgiving at temperatures in which cells thrive.

Steroids: Here to Pump You Up?

Our final molecule in the lipid fatty trifecta is cholesterol. As you may have heard, there are a few different kinds of cholesterol, some of which we consider to be “good” and some of which is “bad.” The good cholesterol, high-density lipoprotein, or HDL, in part helps us out because it removes the bad cholesterol, low-density lipoprotein or LDL, from our blood. The presence of LDL is associated with inflammation of the lining of the blood vessels, which can lead to a variety of health problems.

But cholesterol has some other reasons for existing. One of its roles is in the maintenance of cell membrane fluidity. Cholesterol is inserted throughout the lipid bilayer and serves as a block to the fatty tails that might otherwise stick together and become a bit too solid.

Cholesterol’s other starring role as a lipid is as the starting molecule for a class of hormones we called steroids or steroid hormones. With a few snips here and additions there, cholesterol can be changed into the steroid hormones progesterone, testosterone, or estrogen. These molecules look quite similar, but they play very different roles in organisms. Testosterone, for example, generally masculinizes vertebrates (animals with backbones), while progesterone and estrogen play a role in regulating the ovulatory cycle.

Double X Extra: A hormone is a blood-borne signaling molecule. It can be lipid based, like testosterone, or short protein, like insulin.

Proteins

As you progress through learning biology, one thing will become more and more clear: Most cells function primarily as protein factories. It may surprise you to learn that proteins, which we often talk about in terms of food intake, are the fundamental molecule of many of life’s processes. Enzymes, for example, form a single broad category of proteins, but there are millions of them, each one governing a small step in the molecular pathways that are required for living.

Levels of Structure

Amino acids are the building blocks of proteins. A few amino acids strung together is called a peptide, while many many peptides linked together form a polypeptide. When many amino acids strung together interact with each other to form a properly folded molecule, we call that molecule a protein.

For a string of amino acids to ultimately fold up into an active protein, they must first be assembled in the correct order. The code for their assembly lies in the DNA, but once that code has been read and the amino acid chain built, we call that simple, unfolded chain the primary structure of the protein.

This chain can consist of hundreds of amino acids that interact all along the sequence. Some amino acids are hydrophobic and some are hydrophilic. In this context, like interacts best with like, so the hydrophobic amino acids will interact with one another, and the hydrophilic amino acids will interact together. As these contacts occur along the string of molecules, different conformations will arise in different parts of the chain. We call these different conformations along the amino acid chain the protein’s secondary structure.

Once those interactions have occurred, the protein can fold into its final, or tertiary structure and be ready to serve as an active participant in cellular processes. To achieve the tertiary structure, the amino acid chain’s secondary interactions must usually be ongoing, and the pH, temperature, and salt balance must be just right to facilitate the folding. This tertiary folding takes place through interactions of the secondary structures along the different parts of the amino acid chain.

The final product is a properly folded protein. If we could see it with the naked eye, it might look a lot like a wadded up string of pearls, but that “wadded up” look is misleading. Protein folding is a carefully regulated process that is determined at its core by the amino acids in the chain: their hydrophobicity and hydrophilicity and how they interact together.

In many instances, however, a complete protein consists of more than one amino acid chain, and the complete protein has two or more interacting strings of amino acids. A good example is hemoglobin in red blood cells. Its job is to grab oxygen and deliver it to the body’s tissues. A complete hemoglobin protein consists of four separate amino acid chains all properly folded into their tertiary structures and interacting as a single unit. In cases like this involving two or more interacting amino acid chains, we say that the final protein has a quaternary structure. Some proteins can consist of as many as a dozen interacting chains, behaving as a single protein unit.

A Plethora of Purposes

What does a protein do? Let us count the ways. Really, that’s almost impossible because proteins do just about everything. Some of them tag things. Some of them destroy things. Some of them protect. Some mark cells as “self.” Some serve as structural materials, while others are highways or motors. They aid in communication, they operate as signaling molecules, they transfer molecules and cut them up, they interact with each other in complex, interrelated pathways to build things up and break things down. They regulate genes and package DNA, and they regulate and package each other.

As described above, proteins are the final folded arrangement of a string of amino acids. One way we obtain these building blocks for the millions of proteins our bodies make is through our diet. You may hear about foods that are high in protein or people eating high-protein diets to build muscle. When we take in those proteins, we can break them apart and use the amino acids that make them up to build proteins of our own.

Nucleic Acids

How does a cell know which proteins to make? It has a code for building them, one that is especially guarded in a cellular vault in our cells called the nucleus. This code is deoxyribonucleic acid, or DNA. The cell makes a copy of this code and send it out to specialized structures that read it and build proteins based on what they read. As with any code, a typo–a mutation–can result in a message that doesn’t make as much sense. When the code gets changed, sometimes, the protein that the cell builds using that code will be changed, too.

Biohazard!The names associated with nucleic acids can be confusing because they all start with nucle-. It may seem obvious or easy now, but a brain freeze on a test could mix you up. You need to fix in your mind that the shorter term (10 letters, four syllables), nucleotide, refers to the smaller molecule, the three-part building block. The longer term (12 characters, including the space, and five syllables), nucleic acid, which is inherent in the names DNA and RNA, designates the big, long molecule.

DNA vs. RNA: A Matter of Structure

DNA and its nucleic acid cousin, ribonucleic acid, or RNA, are both made of the same kinds of building blocks. These building blocks are called nucleotides. Each nucleotide consists of three parts: a sugar (ribose for RNA and deoxyribose for DNA), a phosphate, and a nitrogenous base. In DNA, every nucleotide has identical sugars and phosphates, and in RNA, the sugar and phosphate are also the same for every nucleotide.

So what’s different? The nitrogenous bases. DNA has a set of four to use as its coding alphabet. These are the purines, adenine and guanine, and the pyrimidines, thymine and cytosine. The nucleotides are abbreviated by their initial letters as A, G, T, and C. From variations in the arrangement and number of these four molecules, all of the diversity of life arises. Just four different types of the nucleotide building blocks, and we have you, bacteria, wombats, and blue whales.

RNA is also basic at its core, consisting of only four different nucleotides. In fact, it uses three of the same nitrogenous bases as DNA–A, G, and C–but it substitutes a base called uracil (U) where DNA uses thymine. Uracil is a pyrimidine.

DNA vs. RNA: Function Wars

An interesting thing about the nitrogenous bases of the nucleotides is that they pair with each other, using hydrogen bonds, in a predictable way. An adenine will almost always bond with a thymine in DNA or a uracil in RNA, and cytosine and guanine will almost always bond with each other. This pairing capacity allows the cell to use a sequence of DNA and build either a new DNA sequence, using the old one as a template, or build an RNA sequence to make a copy of the DNA.

These two different uses of A-T/U and C-G base pairing serve two different purposes. DNA is copied into DNA usually when a cell is preparing to divide and needs two complete sets of DNA for the new cells. DNA is copied into RNA when the cell needs to send the code out of the vault so proteins can be built. The DNA stays safely where it belongs.

RNA is really a nucleic acid jack-of-all-trades. It not only serves as the copy of the DNA but also is the main component of the two types of cellular workers that read that copy and build proteins from it. At one point in this process, the three types of RNA come together in protein assembly to make sure the job is done right.

Today’s post is long. It’s long because it involves the winding path that science can take from ignition to exploding into the public view… and how the twists and turns in that path can result in a skewed representation and understanding of the science. Read the whole thing. It focuses on an example that involves autism–which seems to pop up in skewed representations every day–but certainly this path from science to you, the consumer, happens with scientific information in general. The author is Jess, who blogged this originally at “Don’t Mind the Mess” and graciously gave us permission to reproduce it here. Jess, an attorney with a B.S. in biochemistry, parent of an autistic child and brand new baby, and self-described “Twitter fiend,” tweets as @JessicaEsquire.

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I am putting my foot down.

As the parent of an autistic child I hear a lot about vaccines and about half a million other things that people think cause autism.

I’m hyperaware of the attention autism gets in the media. So I know about the CDC’s new stats on autism rates. I know about the debate on whether the increase in autism is due to more awareness and diagnosis or more actual occurrences. (Personally, I find the former to be a serious factor, though who’s to say how much.) And I see all the articles that come out week after week about the millions of things that are linked to autism.

There’s a recurring problem here. Valuable research is done. Research is disseminated. Information is reported. Articles are read. Findings are spread. What starts in a lab ends up in a Facebook status. What starts as truth ends up as mistruth in something like a child’s game of telephone. Along the way, piece by piece, truth fades away in favor of headlines and pageviews and gossip.

It’s getting just plain stupid. I’m starting to suspect these articles have nothing to do with serious research but with a search for traffic and hype, an attempt to ride the wave of a trendy topic as concerned parents read every horror story they can find.

A particularly egregious one came up recently. This one doesn’t just cite some random correlation. This one is just plain making things up. The problems here just pile one on top of the other. So let’s consider it piece by piece, a case study in how real research becomes misinformation.

Part One: Research

It starts with scientists. It starts with research. They write up their findings and publish them in a peer-reviewed scientific journal. In this case there are several papers published over a few years about chemicals and their link to brain development. They cover a wide variety of issues and present a wide variety of conclusions. All of them suggest further study.

Maybe they have bad methodology or use statistics incorrectly. Only a few people would ever know the difference. That’s not my concern today. Bad science is one thing, but bad information on good science is another. So let’s assume we have good, solid science in this research.

Part Two: The Conference

Scientists and researchers with similar interests get together and discuss their findings. It’s not that difference from any other conference. There are panels and presentations.

Part Three: The Op-Ed

Next, a group that works on environmental hazards for children publishes a paper. Not a research study but an op-ed in a peer-reviewed journal. In this op-ed they review the conference from Part Two and encourage the study of environmental factors and their relationship to neurodevelopment disorders. Autism is one of many neuro-ish disorders and is mentioned by name in the piece and its title. It’s unclear to me why they zero in on autism. They have a couple vague pieces of evidence that are autism-specific, but the vast majority of what they’re looking at has never been demonstrated to have any kind of relationship to autism, not even a correlation.

Problem #1 is the unnecessary autism name-checking. Problem #2 is much worse, it’s the list of 10 chemicals they suggest for future study. The list itself isn’t a bad idea, I guess. They’re suggesting places for potential research, which certainly needs to be done. But it does reek a little bit of the kind of thing magazines do, you know what I mean, 10 Ways To Get Your Guy All Fired Up! and such. Still, it’s their prerogative.

So let’s examine their evidence for these suggestions. They cite at least one paper for each of these chemicals. I checked them all. The vast majority of them have never shown any connection to Autism (or even ADHD, another diagnosis they name-check). In fact, many of them show that with exposure to these chemicals, the outcome differentials between exposure and non-exposure is 5 IQ points.

FIVE IQ POINTS. Statistically significant? Perhaps. Practically important for a parent? No.

IQ itself is a strange and vague thing. And 5 points isn’t going to move your super-genius down to the level of an average person They’d still be a super-genius. And adding 5 points to someone with severe deficits isn’t going to make them average, either. It’s hard to imagine what difference you’d see between two people whose IQ’s are 5 points apart.

Such statistical differences may well be a sign to warrant further study. And they may be a sign that these chemicals affect neurological development. But it’s getting a bit ahead of ourselves to say they are suspected of being tied to autism. Many of these papers are in areas of research that are just beginning. Many of them involve homogeneous groups (for example, all the participants are Mexican-American migrant workers) which makes issues of genetics and heredity very difficult to account for. Many involve parents self-reporting by filling out surveys rather than having the children examined by professionals.

Let’s be fair. These are the very beginnings of research. You’ll need to do all sorts of rigorous testing and consideration to make real connections. Of course more research is needed. And it’s important that we keep that in mind as we move forward.

(Though, of course, no one else will.)

Part Four: The Press Release

The op-ed is about publicity so it’s the beginning of the problem. But it gets worse.A press release comes out with the list of ten chemicals and already the twisting starts. These are chemicals suggested for further research, but suddenly they’re a ”List of the Top Ten Toxic Chemicals Suspected to Cause Autism and Learning Disabilities.” This, unsurprisingly, is the headline you’ll see all over the internet when news organizations report on the press release. Already it’s turned from suggestions for research into a watchlist.

It gets worse. The press release has this second headline:

The editorial was published alongside four other papers — each suggesting a link between toxic chemicals and autism.

No, actually that’s not at all accurate.

Let’s start with the first paper, which examines the possibility of a connection between maternal smoking and autism. What’s their conclusion?

The primary analyses indicated a slightly inverse association with all ASDs[.]

What does that mean? Among the autistic kids vs. regular kids, there was actually LESS maternal smoking in the autism group. The paper does point out that when it comes to “subgroups,” for instance high-functioning ASD or Asperger’s, there may be a possibly positive relationship. But there are so many caveats I can’t even get to them all. Let’s just take this one:

The ASD subgroup variables were imperfect, relying on the child’s access to evaluation services and the documentation by a myriad of community providers, rather than direct clinical observation.

This means that when they’re saying some groups of ASD kids may have this relationship, they didn’t actually classify these kids. They never saw these kids. They’re relying on data collected by other people. Not even by a consistent set of people. It comes from 11 different states and who knows how many providers. Who’s to say how accurate any of it is. And who’s to say whether these kids are correctly classified at their particular place on the spectrum.

So take all that with a whole jar full of salt and you’re still looking at, overall, no connection with smoking. If anything, the data would indicate smoking has LESS autism rather than more.

After this there are 2 papers on the same chemical. One of them does not contain the word “autism” anywhere. (One of its references has it, but nowhere does it appear in the text of their paper.) The second paper is better. It focuses on the chemical’s effects in particular processes which have been linked to autism. This is very micro-scale science, there are no people involved, just cells and chemicals. It’s important research, but there’s a long stretch between cellular interactions and a person’s diagnosis. It didn’t involve any analysis with autistic individuals. This is certainly the most useful paper of the bunch by a long shot, but it still just sets the stage for further research.

The fourth paper is a review. That means it asserts no new information but summarizes the research on a particular issue, specifically pesticides and autism. Technically I suppose it does assert a link, but none of this is new information.

So I think we’ve pretty much destroyed the headline in that press release. There were not 4 articles suggesting a connection between chemicals and autism.

Is it likely that the writers who take this press release and write articles on it are going to read the papers it cites? Are they going to realize that what they’re saying isn’t actually true? They should. Of course they should. But they don’t.

This list has chemicals suspected of being tied to neurological development. And we should just leave it at that. It’s not that they shouldn’t be studied. They should. But we shouldn’t be throwing out buzzwords like ADHD and Autism when the research doesn’t show any firm data.

Part Five: News Articles

This is a process, though. First research, then op-ed, then press release and finally news articles. So what’s the headline of our news article? “Top 10 Chemicals Most Likely to Cause Autism and Learning Disabilities.” Guilty of serious fearmongering, no? A more accurate title may be: Researchers propose list of chemicals potentially tied to neurological development for further study. But I doubt anyone’s going to write that.

The article itself, to be fair, is full of caveats. The reasons for the increase in autism are “controversial.” There is a “gap in the science.” But then you get a sentence like this:

But clearly, there is more to the story than simply genetics, as the increases are far too rapid to be of purely genetic origin.

Clearly? Clearly says who? What source says it’s too rapid? The author certainly isn’t a reliable source. She is Robyn O’Brien, a writer for Prevention who posted this article. Her scientific credentials are nonexistent. She is a former financial analyst who now writes about the food industry. She has an MBA, and her undergraduate was in French and Spanish.

Full disclosure: I have a B.S. in Biochemistry, but I feel I’m unqualified to write this article. I’d much rather it be written by someone with a PhD. I’m married to a PhD, which has given me a lot more exposure to science since leaving school, but I fully acknowledge that I shouldn’t be the one doing this. I know how to read a scientific article and examine its conclusions, but I certainly am not someone who can tell you if their methods and analysis are correct.

But I’m talking because there aren’t enough people talking about it. Because the PhD’s aren’t generally science writers. They are scientists. They write about their research in journals, not in the newspaper. And certainly not on a blog for a healthy living magazine.

The author goes on to restate the inaccurate subheadline of the press release verbatim.

In the end she suggests things like buying organic produce, opening your windows and buying BPA-free products.

This is part 5 of our process, but it’s where many of us start. Many of us will only read this article and not the press release or the op-ed or the research papers. Most of us aren’t qualified to do so, all we have is this article. Well, we have that and what other people tell us. Which leads us to our next step.

Part Six: Readers

The article is frustrating, but I can only get so mad. She is saying what the scientists told her to say. She has even included some cautionary language. The problem is that when writing for laymen, you have to be careful.

And with AUTISM? You have to be really careful. Just for you I’m going to venture into the comments to this article to show you how people have responded.

–How about we quit injecting our kids with aluminum, formaldehyde and the rest of the toxic stew that they call vaccines — we bypass every natural defense our bodies have (skin, saliva, stomach acid) to put these things directly in the blood stream.

–What about heavy metals like Arsenic that are trapped in soils that our “organic” brown rice is growing in to be made into brown rice syrup to sweeten organic foods and baby formula? Not to mention the reports coming in regarding the radiation and contamination from Fukushimi that has reached the west coast an is spreading across this country in the produce and even the pollen…

–Unvaccinated children are some of the healthiest little people on the planet. As far as the Autism link, who really knows but why risk it.

–Thank you for this information. It confirms to me that we should keep doing what we are doing. It also helps me to enforce our no shoes policy in our home. Some people are so disrespectful and just don’t take them off and I hate to sound like a nag and ask even though they already know its what we prefer.

Thankfully there are some people in there who take the writer to task, but how is a reader to trust any one commenter over another? You have no way of knowing from a comment what someone’s experiences or qualifications are.

There’s a reason we need responsible scientific reporting. I’m all for the open dissemination of information, but I’m also aware of what happens when people read something they don’t understand.

I encountered this FB conversation the other day. Usually I overlook such things but I could not help myself. I jumped in. I tried hard to be polite and present facts. When all that was over, no one was convinced. The response?

Enough articles on vaccines and people are scared even without evidence. Enough headlines and people don’t bother reading articles. It doesn’t matter how much is retracted or debunked, the damage is done.

We need responsible science reporting. We need responsible reporting, period. I’ve seen plenty of lazy articles on Supreme Court opinions that lead me to read the opinion myself only to realize that they’ve stated the conclusions all wrong.

I don’t want to go on all day, but I do feel like it’s important for us to put our foot down and demand better.

We aren’t all scientists. But we can ask for science writers with the appropriate qualifications. We can ask for links and citations in their articles. (I spent quite some time tracking everything down for this post, and luckily I’m relatively familiar with looking up scientific articles online.) We can ask for articles that show failed connections. It doesn’t all have to be “Autism linked to X” there’s plenty of “Autism not linked to Y” that happens in these studies but you never see that, do you?

As for us laymen, we have to find our own trusted experts. Ask your pediatrician. And if your pediatrician’s not qualified (most of them are MD’s but not PhD’s) ask them if they have a trusted source. Track down specialists in Autism with PhD’s and ask them what they think of the research. Find reliable books and articles and spread them to your friends. We can’t necessarily do a lot, but we can do our part to stop the spread of misinformation and demand better.

These views are the opinion of the author and do not necessarily either reflect or disagree with those of the DXS editorial team.

For decades, biology textbooks have stated this as fact: “Women are born with all the eggs, or oocytes they will ever have.”1 The assumption — which shapes research on infertility and developmental biology, as well as women’s mindsets about their biological clocks — is that as women age, they use up those reserves they are born with. With each menstrual cycle, egg by egg, the stockpile wears down.

But is it true that women can’t produce any new oocytes in their adult life? Over the past decade, some scientists have begun to question the long-held assumption, publishing evidence that they can isolate egg-producing stem cells from adult human ovaries.

Last week, biologist Allan Spradling of the Howard Hughes Medical Institute and Carnegie Institution for Science, cast a shadow over those findings with a new analysis of the ovaries of adult female mice, which have similar reproductive systems to humans. By his measures of new egg formation, which he has previously studied and characterized during fetal development, there were no signs of activity in the adults.

“Personally, I think it’s quite clear,” says Spradling. “All the evidence has always said this. When oocyte development is going on, you see cysts everywhere. When you look at adults, you don’t see any.”

An oocyte, or egg cell, surrounded by some supporting cells.

The new paper does little to change the direction of those researchers already pursuing the stem cells, though. Jonathan Tilly of Massachusetts General Hospital was among the first to publish evidence that mice and human females have adult germ-line stem cells that can make new eggs.

“There’s so much evidence now from so many labs that have purified these cells and worked with these cells,” says Tilly. “What I don’t find of value is to say these cells don’t exist.”

For now, the two sides remain fractured — Spradling sees weaknesses in the way Tilly and others have isolated cells from the ovaries and suspects that the properties of the cells could change when they’re outside the body. And Tilly proposes that Spradling’s new data could be interpreted in a different way that in fact supports the presence of stem cells.

For women hoping for a scientific breakthrough to treat infertility — or even those simply curious about how their own body works — a consensus on the answer would be nice. But the continued probing on both sides may be just as much a boon to women’s health. After all, it’s questions like these that drive science forward.

In his new study, Spradling labeled a spattering of cells in the ovaries of female mice with fluorescent markers to make them visible and watched them as the mice aged. If any labeled cells were egg-producing stem cells, he says, they would spread the fluorescence as they made clusters of new eggs.

“But you never see clusters,” Spradling says. “Not once.”

In the process of this study, though, Spradling made new observations about how egg cells develop into their final form in female mice, published in a second paper this month. As the precursor cells to eggs mature, they lump together into cysts, a phenomenon also seen in the flies that Spradling has spent decades studying. In flies, one cyst eventually forms one egg. But in the mice, he discovered, those cysts break apart and form multiple eggs.

“This actually leads us to propose a new mechanism for what determines the number of oocytes,” says Spradling. And, of course, that means a better understanding of reproductive biology.

On the side of those who are confident about the existence of adult ovarian stem cells, the field of fertility medicine could be revolutionized if the cells that Tilly has isolated from ovaries can form healthy egg cells that can be fertilized in vitro. These stem cells could also be a tool to study more basic questions on oocyte development and formation or a screening platform for fertility drugs. Tilly is confident enough in the research that he has founded a company, OvaScience, to pursue the commercial and clinical potential of isolating the stem cells.

“The value for the lay public is that we have a new tool in our arsenal,” says Tilly.

Spradling doesn’t argue that continued research in this area isn’t a good thing. “Scientific knowledge doesn’t just come from the proposal of ideas, but also from their rigorous tests,” he says. “I think the most powerful tool we have in medical science is basic research,” he adds, referencing research using cell and animal studies. Investigations of the basics of how and when oocytes form, he says, are the best way forward toward developing ways to improve egg cell formation or development and could even lead to infertility treatments.

So if it finds support from further studies, Spradling’s new work — which states bluntly right in its title that “Female mice lack adult germ-line stem cells” — needn’t be seen as bad news for those dreaming of a breakthrough in understanding fertility. Instead, whether or not egg stem cells end up having clinical value, it’s a step forward in advancing understanding about women’s reproductive biology.

As Spradling puts it: “You have a much better chance of actually helping someone with infertility if you know what the real biology is. Right now, we’re a ways from really understanding the full biology, but we’re making progress.”

1 Direct quote from the third edition of “Human Physiology: An Integrated Approach”, one published by Pearson Education in 2004 and used in medical school classes. Continue reading →